Recently, the United States Food and Drug Administration published a series of product-specific guidance for the development of topical drugs, with in vitro options consisting of qualitative sameness (Q1) and quantitative sameness (Q2) assessment of formulations, physiochemical and structural characterization of formulations (Q3), and, potentially, in vitro drug release and permeation tests. In these tests, the topical semisolid product’s critical quality attributes (CQAs), such as rheological properties, thermodynamic activity, particle size, globule size, and rate/extent of drug release/permeation, are evaluated to ensure the desired product quality. However, alterations in these CQAs of the drug products may occur under ‘in use’ conditions because of various metamorphosis events, such as evaporation that leads to supersaturation and crystallization, which may eventually result in specific failure modes of semisolid products. Under ‘in use’ conditions, a limited amount of formulation is applied to the skin, where physicochemical characteristics of the formulation are substantially altered from primary state to secondary and, eventually, tertiary state on the skin. There is an urgent need to understand the behavior of topical semisolid products under ‘in use’ conditions. In this review, we attempt to cover a series of metamorphosis events and their impact on CQAs (Q3 attributes), such as viscosity, drug activity, particle size, globule size, and drug release/permeation of topical semisolid products.

Facile and sensitive detection methods of cancer cells in the early stage are beneficial for monitoring cancers and treating patients in time to reduce the death rate. In this work, an ultrasensitive cytosensor was constructed using aptamers as cell capturers and metal ion-exchanged titanium phosphate nanospheres as electrochemical probes. KH1C12 can specifically recognize HL-60 cells and distinguish them from other cell lines, K562 and CCRF-CEM, to obtain high selectivity. Cadmium ion functionalized titanium phosphate nanospheres show large quantities of electroactive cadmium ion output and a highly sensitive electrochemical signal. This proposed cytosensor showed a wide dynamic linear range from 102 cells per mL to 107 cells per mL with a low detection limit of 35 cells per mL, providing a new, simple and ultrasensitive platform for cancer diagnosis in biomedical and clinical research.

Apart from well-known respiratory symptoms, less frequent symptoms also appear as a direct result of COVID-19 infection, or as indirect effects of the recommended quarantine and related lifestyle changes. The impact of the COVID-19 pandemic on human skin is predominantly focused on in this article. Cutaneous manifestations, including redness, chilblain-like symptoms (COVID toes), hives or urticaria rash, water blisters, and fishing net-like red-blue patterns on the skin, may appear as accompanying or as systemic COVID-19 symptoms with potential lesions at different skin sites. These symptoms were related to skin phototypes and vitamin D deficiency. Moreover, Black, Asian, and minority ethnic origin patients are found to be more sensitive to COVID-19 infection than Caucasians because of vitamin D deficiency. The region of population with lighter skin phototypes have a significantly higher chance to develop cutaneous manifestations than population with dark skin. In addition, adverse effects, such as skin barrier damage and irritation, may also occur due to extensive personal protective equipment usage (e.g., masks, protective suits, and a few others) and predominately alcohol-based sanitizers. This manuscript covers various aspects of COVID-19 and its clinical skin manifestations.

When developing topical semisolid products, it is crucial to consider the metamorphosis of the formulation under the “in use” condition. Numerous critical quality characteristics, including rheological properties, thermodynamic activity, particle size, globule size, and the rate/extent of drug release/permeation, can be altered during this process. This study aimed to use lidocaine as a model drug to establish a connection between the evaporation and change of rheological properties and the permeation of active pharmaceutical ingredients (APIs) in topical semisolid products under the “in use” condition. The evaporation rate of the lidocaine cream formulation was calculated by measuring the weight loss and heat flow of the sample using DSC/TGA. Changes in rheological properties due to metamorphosis were assessed and predicted using the Carreau–Yasuda model. The impact of solvent evaporation on a drug’s permeability was studied by in vitro permeation testing (IVPT) using occluded and unconcluded cells. Overall, it was found that the viscosity and elastic modulus of prepared lidocaine cream gradually increased with the time of evaporation as a result of the aggregation of carbopol micelles and the crystallization of API after application. Compared to occluded cells, the permeability of lidocaine for formulation F1 (2.5% lidocaine) in unoccluded cells decreased by 32.4%. This was believed to be the result of increasing viscosity and crystallization of lidocaine instead of depletion of API from the applied dose, which was confirmed by formulation F2 with a higher content of API (5% lidocaine) showing a similar pattern, i.e., a 49.7% reduction of permeability after 4 h of study. To the best of our knowledge, this is the first study to simultaneously demonstrate the rheological change of a topical semisolid formulation during volatile solvent evaporation, resulting in a concurrent decrease in the permeability of API, which provides mathematical modelers with the necessary background to build complex models that incorporate evaporation, viscosity, and drug permeation in the simulation once at a time.